Cover Page The handle

The handle

http://hdl.handle.net/1887/66665

holds various files of this Leiden University

dissertation.

Author: Suzuki, Y.

Title: From the macro- to the microvasculature : temporal and spatial visualization using

arterial spin labeling

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Blood circulation, which delivers oxygen and nutrition by arterial blood, while removing waste products on the venous side, is an essential prerequisite for the survival of biological tissue. Particularly for brain tissue, even a short interruption of the blood circulation can result in critical consequences (1). Because of this great importance, the vascular system has amazing compensatory mechanisms. One of the most important mechanisms is the circle of Willis, which is a circular structure of arteries in the brain allowing collateral blood flow from one hemisphere to the other as well as between the anterior and posterior circulation (2,3). However, when the collateral circulation at the circle of Willis is not sufficient, the pre-existing collateral arterioles start to expand their lumen and eventually result in the development of functional collateral circulation (4-6). This process is induced by increased shear stress following the stenosis/occlusion of a main artery, which is termed arteriogenesis. In contrast, angiogenesis is triggered by tissue hypoxia and results in sprouting of new capillaries. Because these newly generated capillaries do not have vascular smooth muscle cells, they are more fragile.

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stroke. However, because the progression of the steno-occlusion cannot be stopped

by medication, the revascularization surgery is recommended proactively to avoid further ischemic or hemorrhagic events (16,17). Successful restoration of the cerebral blood supply by revascularization can reduce the risks for further events, as well as improving the postoperative activities of daily living (ADL) and long-term prognosis of higher brain functions (16). Therefore, postoperative assessments of revascularization and follow-up are considered very important. Untreated asymptomatic Moyamoya patients (diagnosed before the events) are also considered potentially at risk for future progress and onset of event, thereby requiring careful long-term observation. On the other hand, angiogenesis is also a hallmark of pathological processes, e.g. to supply tumors with oxygen and nutrient rich blood which is needed to support tumor growth (18,19). Perfusion measurements of tumor blood flow provide important information for condition, staging and differentiation of the disease (20-23). For highly vascularized tumors, such as meningioma, preoperative endovascular embolization is often applied before surgical resection to reduce blood loss during surgery (24). In such cases, information about the feeding arteries (e.g. whether the dominant supply is from internal carotid artery or external carotid artery) is useful for treatment planning. Cerebral arteriovenous malformation (AVM) is also an example of a cerebrovascular disease with increased vascularity, in which abnormal, tangled blood vessels connect arteries directly to veins without the presence of a normal capillary bed in between. Such AVMs provided an increased risk of intracranial hemorrhages. General treatment options of AVMs are surgical resection, gamma knife and endovascular embolization, and the optimal treatment is decided upon by taking the anatomic and hemodynamic properties of the AVM (e.g. size and location of nidus, arterial feeders and pattern of the venous drainage) into account.

patients with Moyamoaya disease (the highest peak onset is between 5 to 9 years of age (32)), need numerous diagnostic scans to monitor disease progression and for them establishment of a non-invasive examination without the associated risks of catheter procedures, anesthesia or contrast agent injections would be highly desirable. Moreover, the recently found accumulation of Gadolinium in the brain is another urgent reason to develop non-invasive alternatives.

This doctoral thesis describes the development of several new techniques for dynamic MRA (4D-MRA) and perfusion imaging based upon ASL MRI. The purpose of those developments is to implement clinically useful and feasible techniques, while being as patient-friendly as possible.

Acceleration of ASL-based dynamic angiography (ACTRESS)

In the last decade, 4D-MRA using ASL has become an important alternative to CE-4D-MRA in the brain, by demonstrating advantages over a CE-CE-4D-MRA examination, such as, needless to say, the ability to visualize arteries without using contrast agent, as well as two other main advantages: firstly, in the acquisition of CE-4D-MRA, it is desired to capture the first passage of the contrast agent bolus by means of a real-time dynamic acquisition. Due to very fast passage of the contrast agent through the vascular tree and the early appearance of venous signal, each dynamic must be acquired very quickly, and therefore spatial resolution is usually compromised. In ASL, on the other hand, the labeling of the arterial blood and following data acquisition can be repeated until sufficient information is acquired for both high spatial and temporal resolution, because it is not necessary to acquire all information during a single passage of the bolus.

It should be noted that, however, the scan time of ASL-based 4D-MRA acquisition is generally much longer than CE-4D-MRA. This is not only because of the repeated acquisition to achieve high spatial and temporal resolution, but also because ASL techniques require the acquisition of two types of images: labeled and control images. Subtraction of these two images eliminates the background static tissue signal, thereby isolating the signal of the labeled blood. As Figure 1 illustrates, labeled and control images are usually acquired in separate Look-Locker cycles, resulting in a doubling of the scan time. In previous studies, the mean scan time of ASL-based 4D-MRA was approximately 7 minutes (5 min – 8.5 min) (33-38), which is not always suitable for clinical use.

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the ACTRESS approach, a single control image is acquired before applying the

labeling pulse followed by multi-phase Look-Locker readout, and all labeled images are subtracted from this single control image (39). This allows 4D-MRA images to be acquired with similar image quality in nearly half the scan time of the conventional ASL-based 4D-MRA acquisition using pulsed ASL (PASL).

Figure 1: A schematic figure of ASL-based 4D-MRA using Look-Locker readout.

Vessel-selective dynamic angiography using vessel-encoded

pseudo-continuous ASL

The second advantage of ASL-based 4D-MRA over CE-4D-MRA is the ability to perform vessel specific visualization, in which the vascular tree arising from a selected artery can be exclusively visualized by means of spatially selective labeling. This technique could provide clinically important information for smoother examination and treatment by X-ray DSA, or even be a potential alternative of X-ray DSA examination for treatment planning and follow-up of many cerebrovascular diseases, such as depiction of collateral flow in patients with steno-occlusive diseases (48) and identification of feeding arteries for AVM (40).

and ECA) is difficult because the labeling slab usually includes the common carotid artery. In contrast, in pseudo-continuous ASL (pCASL), labeling of arterial blood is performed by means of flow-driven pseudo-adiabatic inversion in a thin labeling plane planned perpendicular to the flow direction. Vessel-selective labeling can be achieved by applying additional gradients in the in-plane direction, generating in-plane differences in labeling efficiency. Therefore, pCASL allows vessel-selective planning with very little restrictions and a low risk of partial labeling of blood in untargeted arteries when tortuous vascular anatomy is present.

In chapter 3, a new implementation of vessel-selective 4D-MRA using vessel-encoded (ve) pCASL (41) is proposed. Ve-pCASL consists of several labeling patterns played out according to a Hadamard matrix, instead of pair-wise acquisition of labeled and control images. For successful implementation, there are two hurdles to overcome. First, the scan time of 4D-MRA using ve-pCASL will increase proportionally to the number of Hadamard-encodings. For perfusion imaging, the acquisition of different encodings can be performed instead of signal averaging, therefore vessel-selective imaging can be achieved without extra scan time or loss in signal to noise ratio (SNR). However, this is not true for an MRA acquisition, because in ASL-based MRA the entire scan time is usually spent to obtain high spatial resolution, rather than signal averaging. In this study, therefore, separate visualization of three arterial trees arising from the right ICA (RICA), left ICA (LICA) and both vertebral arteries (VAs) is proposed by using four Hadamard-encodings, to minimize the scan time. The measured signal in this study can be written as follows:

-1 1 1 -1 RICA LICA VAs S 1 1 -1 -1 1 -1 1 -1 1 1 1 1 y =

_[1]

where y is the measured signal and S is static tissue. Each arterial tree arising from RICA, LICA and VAs is calculated by applying the pseudo-inverse matrix of equation [1].

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broad and flat enough, thereby increasing the risk of partial labeling of non-targeted

arteries, which will compromise the accurate separation of the arterial trees in the selective angiograms. In this chapter the shape of the spatial inversion modulation is optimized by changing the pCASL labeling parameters (maximum and mean labeling gradient strength), so that a sharper transition between the labeling and control conditions and broader, flatter control regions can be achieved. This enables the acquisition of ve-pCASL 4D-MRA in half the time of previous implementations (42).

Acceleration of vessel-selective dynamic angiography using the

ACTRESS approach

When considering the separate visualization of the ICA and the ECA, applying ve-pCASL with four Hadamard encodings will be difficult due to the number of arteries that need to be differentiated and their location with respect to each other. Instead of ve-pCASL scan, therefore, a simple one-by-one labeling of ICA and ECA might be easier to obtain the desired information. However, a pair-wise acquisition of labeled and control images for each target artery will be time-consuming.

Moreover, there is another inconvenience caused by the long pCASL labeling train. Unlike the PASL technique that relies on a very short labeling pulse (approximately 10-20 ms), the pCASL labeling train lasts from hundreds to thousands of milliseconds, after which the front of the bolus of labeled blood will already have reached the peripheral arteries. Therefore, the conventional subtraction would only depict the outflow of labeled blood.

In this study, a WET pre-saturation module (43) was inserted before the pCASL labeling train to minimize the signal variation of the static tissue over the Look-Locker acquisitions. Moreover, a new subtraction scheme was introduced to depict arteries with wide range of temporal information from the early inflow to the late peripheral phase.

Simultaneous acquisition of 4D-MRA and perfusion images

using time-encoded pCASL

For assessment of the hemodynamic condition of brain tissue, it is essential not only to visualize large vessel pathology, such as stenosis or collateral flow, but also to know the microvascular status of downstream tissue, i.e. quantitative information on the cerebral perfusion of the tissue. However, including both acquisitions of 4D-MRA and perfusion imaging into a clinical protocol would be hampered by long scan time. To address this issue, in chapter 5, the development of a simultaneous acquisition scheme of 4D-MRA and perfusion imaging is described.

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In chapter 5, we propose the use of time-encoded pCASL (te-pCASL) to obtain the

different temporal information for the 4D-MRA and perfusion image (44). Unlike the Look-Locker readout that was used in previous chapters, in te-pCASL images with N delays are obtained by dividing the long pCASL labeling train into N segments (a.k.a. subboli) with either a label or a control condition. The acquisitions are repeated N+1 times, with different combinations of label/control condition according to a Hadamard matrix of order N+1 (N=7 in Figure 2). By employing the appropriate decoding step, only the ASL signal from a single subbolus can be reconstructed, i.e. N ASL images with different post-labeling delays (PLDs) are obtained. In this study, the first subbolus was optimized for perfusion imaging with a long labeling duration and a PLD of 1.8 sec, whereas the other subboli were optimized for 4D-MRA with relatively short labeling durations to achieve a high temporal resolution as desired in 4D-MRA.

Figure 2: A schematic figure of time-encoded (te) pCASL.

ASL perfusion imaging with simultaneous multi-slice EPI

acquisition

There is another factor why ASL signal in perfusion imaging is much lower compared to 4D-MRA: during the delay time that allows all labeled arterial blood to arrive in the brain tissue, the ASL signal will decrease with the T₁ relaxation of the blood. In general, a PLD of 1.8 to 2 seconds is recommended for adult examinations, because too short PLD would not only cause an underestimation of the perfusion signal, since not all labeled arterial blood has arrived yet, but also cause hyperintense vascular artefacts from arteries where labeled blood is still present.

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